1. Field of the Invention
The invention related to analogs of parathyroid hormone.
2. Brief Description of Related Art.
Parathyroid hormone (PTH) regulates the level of calcium in blood plasma by exerting, inter alia, anabolic and catabolic effects on the skeleton and also by promoting calcium re-absorption by the kidneys. There is reason to believe that the bone-building effect of PTH can be exploited for the clinical treatment of osteoporosis; see J. Bone Mineral Res., 1 (1987 ) 377-382.
There are also indications that the multiple functions of PTH are exerted by different regions of the hormone molecule. For example, it has been found that the N-terminal 34 amino acids mediate the binding of the hormone to its kidney cell receptor with subsequent stimulation of adenylate cyclase (see Adv. Prot. Chem., 32 (1982) 323-395) but that a mitogenic effect originates from the central region sequence 28-48 (see DE-A-37 25 319.0) which effect is not mediated by adenylate cyclase but possibly by protein kinase C. It would therefore seem attractive to modulate individual hormone effects by controlled variation of the amino acid sequence of PTH or of PTH fragments and thus possibly to reduce the catabolic activity of the hormone or increase its anabolic activity.
With regard to the prior art, reference should also be made to U.S. Pat. Nos. 4,086,196 and 4,423,037 and John et al., in Adv. Prot. Chem., 32 (1982) 323.